20 April 2007
US FDA Approves Initial Human Vaccine against H5N1 (Clade 1) Avian Influenza Virus for the Strategic National Stockpile (SNS)
This week the Food And Drug Administration (FDA) announced approval of the first human vaccine to prevent infection with the H5N1 avian influenza virus. This vaccine is made by sanofi pasteur, Inc., and will be manufactured in Swiftwater, Pennsylvania. It will not be available commercially. Instead, it will be purchased by the US government for storage in the Strategic National Stockpile (SNS) for potential future use for prioritized recipients.
In a press release on April 17, the FDA Commissioner, Dr. Andrew C. von Eschenbach stated: “The threat of an influenza pandemic is, at present, one of the most significant public health issues our nation and world faces. The approval of this vaccine is an important step forward in our protection against a pandemic.” www.fda.gov/bbs/topics/NEWS/2007/NEW01611.html
Although generally well tolerated in terms of side effects (e.g., pain at the injection site, headache, muscle pain, and “a general ill feeling”, according to the FDA) by the approximately 400 healthy adult volunteers, the immune responses induced by the vaccine were less than optimal. For example, only 45% of the vaccines who received the highest dose of the vaccine (90 micrograms of H5N1 antigen), intramuscularly on two occasions one month apart, produced antibody levels (titers) considered to be protective against human influenza infection. Thus, this vaccine is a starting point from which to compare future H5N1 vaccines.
This initial H5N1 human vaccine does not include any vaccine adjuvant, such as alum or MF-59. Also of potential importance, it uses a Clade 1 form of the H5N1 virus that was prevalent during the early outbreaks in 2003-2004 in Vietnam and Thailand. More recent outbreaks in 2005-2006 in other nations have involved predominantly a Clade 2 form of the virus (and subclades of Clade 2, according to the WHO H5N1 avian flu website postings). Clade 2-based H5N1 vaccines have already begun to be developed, but none are published yet in the medical literature.
Writing on the vaccine’s approval in the New York Times on April 18, 2007 (page A21), Andrew Pollack quoted Norman Baylor, head of the vaccine office at the FDA as describing this vaccine as an “interim measure”, and that future H5N1 vaccines would hopefully have higher than 45% efficacy, and ideally only require one shot and less H5N1 antigen.
The vaccine’s efficacy is estimated based on the antibody levels produced by the immune response after two shots of the vaccine. No human volunteers were exposed to the actual H5N1 virus after receiving either the vaccine or the placebo. It would be considered unethical to expose human volunteers to a virus that currently has approximately a 60% mortality rate based on the nearly 300 persons with laboratory-confirmed H5N1 virus infections reported by the World Health Organization (WHO).
The initial publication in the medical literature regarding this vaccine was 13 months ago in the March 30, 2006 issue of the New England Journal of Medicine.
Director, Center for Biologic Counterterrorism and Emerging Diseases
EROne Institutes, Department of Emergency Medicine
Washington Hospital Center, Washington, DC
Adjunct Professor of Microbiology and immunology
Georgetown University Medicine Center